ABSTRACT
Background: Carcinoma of the head of pancreas has a high malignant degree and the 5-year survival rate at 5%. For unresectable pancreatic cancer, the 5-year survival rate is even lower. The clinical diagnosis of pancreatic cancer is difficult, and surgical indications are difficult to grasp. Moreover, perioperative and postoperative management is complex, and patients with different conditions need more attention to implement a comprehensive diagnosis and treatment strategy. In the diagnosis and treatment of pancreatic cancer and even other cancers, multi-disciplinary diagnosis and treatment can provide reasonable, personalized and more effective plans for patients so that cancer patients can receive better treatment and improve their quality of life. The multi-disciplinary diagnosis and treatment model can respond to the complex needs to individual patients. Case Description: This model is designed according to each patient's comprehensive situation, including their clinical symptoms, biochemical indicators, body mass index, and psychological status, and the tumor position, pathological tissue typing, and invasion scope. Complications of tumors can be reduced if treatment is controlled and if radical treatments are used within a broader comprehensive care model, thereby improving the quality of life of patients to prolong their survival. In our case report, the overall survival is much longer than un-resectable pancreatic cancer (median overall survival 6-9 months. The female patient was 53 years old. Her chief complaints were yellow skin, yellow urine, and absorption emaciation for 1 month. The preliminary diagnosis was postoperative pancreatic cancer. CT reexamination suggested portal vein liver metastasis. Repeated gastrointestinal bleeding occurs over the course of the disease. Postoperative review suggested recurrence, and she was admitted to First Affiliated Hospital, Army Medical University. During the treatment, the disease progressed to gastrointestinal bleeding, ascites, and jaundice. Conclusions: After multidisciplinary treatment (MDT) discussion, targeted treatment strategies were developed to improve the symptoms and improve the quality of life of the patients.
ABSTRACT
The expressions of ß1,3-N-acetylglucosamonyltransferase-2 and -8 (ß3GnT-2, ß3GnT-8),-the two main glycosyltransferases responsible for the synthesis of poly-N-acetyllactosamine (polyLacNAc) in glycans, and ß3GnT-5 participating in the syntheses of sphingoglycolipids were studied in leukemia cell lines during differentiation using RT-PCR method. ß3GnT-2 and ß3GnT-8 distribute widely in six myeloid and monocytoid leukemia cell lines with different abundances, while ß3GnT-4 was only present in NB4 cells. ATRA (all-trans retinoic acid) and dimethylsulfoxide (DMSO), which induce the differentiation of HL-60 and NB4 (two human acute myeloid leukemia cell lines) to myelocytic lineage, up-regulated these two enzymes with various degrees at 2 and 72 h of treatment. In HL-60 cells treated with ATRA, the increase of ß3GnT-8 was more than ß3GnT-2, while in NB4 cells treated with DMSO, the increase of ß3GnT-2 was more than ß3GnT-8. However, when HL-60 and NB4 were differentiated to monocytic lineage induced by phorbol 12-myristate 13-acetate the expressions of ß3GnT-2 and ß3GnT-8 showed no alterations or the increase of expressions was far less than those in myelocytic differentiation. By means of FITC-labeled tomato lectin affinity staining and flow-cytometry, it was found that the product of ß3GnT-2 and -8, polyLacNAc was also increased on the cell surface of HL-60 and NB4 treated with ATRA or DMSO, but unchanged when treated with PMA. These results were in accordance with the up-regulation of the mRNAs of ß3GnT-2 and -8. The expression of ß3GnT-5, however, was not changed both in myelocytic and monocytic differentiations. The difference in the up-regulation of ß3GnT-2 and -8, especially their products may become a useful index to discriminate the myelocytic and monocytic differentiation of leukemia cells.
Subject(s)
Cell Differentiation , Leukemia, Myeloid, Acute/enzymology , Leukemia, Myeloid, Acute/pathology , N-Acetylglucosaminyltransferases/metabolism , Cell Differentiation/drug effects , Cell Line, Tumor , Dimethyl Sulfoxide/pharmacology , Flow Cytometry , Fluorescence , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Leukemic/drug effects , Humans , N-Acetylglucosaminyltransferases/genetics , Polysaccharides/pharmacology , Tetradecanoylphorbol Acetate/pharmacology , Tretinoin/pharmacology , Up-Regulation/drug effectsABSTRACT
The current study demonstrates vanadium plays the role of antitumor, and its antitumor effect is dosage-dependent. N-acetyl-galactosamine-transferase 2 (polypeptide: N-acetyl-α-galactosaminyl-transferases 2, ppGalNAc-T2) is a member of ppGalNAcTs (polypeptide: N-acetyl-α-galactosaminyl-transferases) family, which proves to play a vital role in the tumor emergence and development process. In this study, we focused on ppGalNAc-T2 and vanadium and aimed to determine whether ppGalNAc-T2 is correlated with vanadium's antitumor effect. We discovered that ppGalNAc-T2 changed with the variation of HL-60 cell growth induced by vanadium at mRNA level. Peanut agglutinin (PNA) is an exogenous lectin. PpGalNacT2 can be indirectly recognized by PNA. By means of flow cytometry and immunofluorescent staining, we found the deviation of PNA binding increased significantly at high concentration vanadium. Then we docked one of the possible compound substances of vanadium onto the body, VO(3) (molecular formula O(13)V(4), partial vanadate tetramer) and ppGalNAcT2, and simulated them via molecular dynamics, which showed that VO(3) may inhibit the activity of the enzyme by stemming conformational changes of a key loop of ppGalNAcT2. To sum up, our results suggested that ppGalNacT2 participated in vanadium induced HL-60 cell differentiation, which might be able to provide a new mechanism of vanadium's antitumor effect.
Subject(s)
Cell Differentiation/drug effects , N-Acetylgalactosaminyltransferases/metabolism , Vanadium/pharmacology , Cell Proliferation/drug effects , Flow Cytometry , Fluorescein-5-isothiocyanate/metabolism , Fluorescence , Gene Expression Regulation, Enzymologic/drug effects , HL-60 Cells , Humans , Lectins/metabolism , Models, Molecular , N-Acetylgalactosaminyltransferases/chemistry , N-Acetylgalactosaminyltransferases/genetics , Peanut Agglutinin/metabolism , Pliability/drug effects , Polysaccharides/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Polypeptide N-acetylgalactosaminyltransferaseABSTRACT
The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] on two leukemia cell lines, K562 and SHI-1, and its relation to the expression of different subtypes of polypeptide: N-acetylgalactosaminyltransferase (pp-GalNAc-T) was studied. With morphological and cell flow-cytometric method, it was found that 1,25(OH)(2)D3 induced the differentiation of both leukemia cell lines toward monocytic lineage, but not affected the cell growth and apoptosis. The expressions of different subtypes of pp-GalNAc-T, the initial glycosyltransferase in O-glycan synthesis, were studied with RT-PCR before and after the treatment of different concentrations of 1,25(OH)(2)D3. Among fourteen subtypes of pp-GalNAc-T (T1 approximately T14), K562 cells obviously expressed pp-GalNAc-T2, T4, T5, T7 (T2 was the highest) and SHI-1 cells apparently expressed pp-GalNAcT1, T2, T3 and T4 (T4 was the highest) only. After K562 cells were treated 1, 25(OH)(2)D3 for 72 h, pp-GalNAc-T2, T4, T5, T7 were increased in a dose dependent manner. In contrast, pp-GalNAc-T1 and T2, especially T1, were up-regulated in SHI-1 cells by 1,25(OH)(2)D3, but T3 was unchanged and T4 was down-regulated. The different alterations of pp-GalNAc-Ts in these two cell lines were probably related to the different structural changes of O-glycans during 1,25(OH)(2)D3 induced differentiation.
